Phase 2
N=166
A Study to Evaluate the Safety and Efficacy of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Participants With High Grade Primary Central Nervous System (CNS) Malignancies
Various Advanced Cancer
Bottom Line
View on ClinicalTrials.gov: NCT03130959 ↗Enrolled (actual)
166
Serious AEs
72.9%
Results posted
Apr 2021
Primary outcome: Primary: Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) — 0; 0; 0 Number of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Nivolumab (Biological); Ipilimumab (Biological)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Bristol-Myers Squibb
- Primary completion
- Mar 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) |
0; 0; 0 | — |
| PRIMARY Number of Safety Lead-In Participants With Serious Adverse Events (SAEs) |
7; 6; 8 | — |
| PRIMARY Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation |
3; 4; 2 | — |
| PRIMARY Overall Survival (OS), Cohort 1 Only |
11.66; 10.78 | — |
| PRIMARY Progression-Free Survival (PFS), Cohorts 2-4 |
1.74; 1.31; 1.38; 2.76; 1.41; 4.60 | — |
| PRIMARY Progression-Free Survival (PFS), Cohort 5 Only |
1.22; 1.61 | — |
| SECONDARY Progression-Free Survival (PFS), Cohort 1 Only |
6.21; 4.53 | — |
| SECONDARY Overall Survival at 12 Months (OS12), Cohorts 1-4 |
47.3; 42.9; 37.5; 32.8; 38.9; 86.7 | — |
| SECONDARY Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 |
9.4; 14.3; 0; 20.0; 20.0; 11.4 | — |
| SECONDARY Overall Survival (OS), Cohorts 2-5 |
6.67; 6.47; 7.36; 22.21; 5.70; 9.82 | — |
| SECONDARY Number of Treated Participants With Adverse Events (AEs) |
23; 21; 15; 14; 14; 15 | — |
| SECONDARY Number of Treated Participants With Serious Adverse Events (SAEs) |
10; 14; 10; 9; 6; 7 | — |
| SECONDARY Number of Treated Participants With Drug-Related Adverse Events |
14; 16; 12; 8; 6; 11 | — |
| SECONDARY Number of Treated Participants With Adverse Events Leading to Discontinuation |
4; 7; 3; 5; 2; 3 | — |
| SECONDARY Number of Treated Participant Deaths |
18; 18; 12; 13; 12; 11 | — |
| SECONDARY Number of Treated Participant With Laboratory Abnormalities - Liver |
3; 7; 2; 0; 0; 3 | — |
| SECONDARY Number of Treated Participant With Laboratory Abnormalities - Thyroid |
2; 1; 3; 1; 3; 7 | — |
Summary
The purpose of this study is to determine the safety and effectiveness of nivolumab alone and in combination with ipilimumab in pediatric patients with high grade primary central nervous system (CNS) malignancies.
Eligibility Criteria
Inclusion Criteria
- Must have received standard of care therapy, and there must be no potentially-curative treatment available, in one of the following cohorts:
- A newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) that has been treated with radiation therapy (RT) but no chemotherapy
- A histologically confirmed recurrent or progressive non-brainstem High Grade Glioma (HGG) previously treated with surgical resection and RT
- A histologically confirmed medulloblastoma that has relapsed or is resistant to at least one line of prior therapy including surgery, RT, and chemotherapy
- A histologically confirmed ependymoma that has relapsed or is resistant to at least one line of prior therapy including surgical resection and RT
- A histologically-confirmed high grade CNS malignancy "other than above" which is recurrent or progressive after at least one line of prior therapy
- Lansky play score (LPS) for ≤ 16 years of age or Karnofsky performance scale (KPS) for > 16 years of age assessed within two weeks of enrollment must be >= 60
- A tumor sample must be available for submission to central laboratory (not required for DIPG)
Exclusion Criteria
- An active, known, or suspected autoimmune disease
- A concurrent condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Other protocol defined inclusion/exclusion criteria apply
Data sourced from ClinicalTrials.gov (NCT03130959). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.